CHICAGO – Hyponatremia quadruples the risk of osteoporosis and fragility fractures, according to a retrospective database study presented at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
A team from Georgetown University in Washington matched 30,517 patients diagnosed with osteoporosis to 30,517 controls for age, race, sex, and how long they had been in the database of the MedStar Health System, which serves Baltimore and Washington.
Dr. Joseph Verbalis
The investigators found that patients with chronic hyponatremia – at least two sodium values below 135 mmol/L at least 1 year apart – were far more likely to be later diagnosed with osteoporosis (adjusted odds ratio, 3.99). Recent hyponatremia – at least one value below 135 mmol/L in the previous 30 days – also increased the risk (aOR, 3.08). In contrast, glucocorticoid use, a known osteoporosis risk factor, was associated with a far lower risk (aOR, 1.4), the team reported in a poster session at the meeting.
The researchers had similar results when they matched 46,256 patients with fragility fractures to 46,256 without: The fracture risk was substantially increased in patients with chronic hyponatremia (aOR, 4.71) and recent hyponatremia (aOR, 3.08). A previous diagnosis of osteoporosis – again, a known risk factor – increased the risk only moderately (aOR, 1.8).
The severity of hyponatremia played a role, too; patients with at least one value below 125 mmol/L had the highest risk for osteoporosis and fragility fractures.
The findings were all statistically significant.
"The results of this study support the hypothesis that hyponatremia is a significant and clinically important risk factor for both osteoporosis and bone fractures in inpatients and outpatients," the team concluded.
"We were surprised by the odds ratios and how strong a factor this was. Right now, hyponatremia is not an indication for bone mineral density [testing] because it’s never been considered to be a risk factor. It ought to be added as an indication. Patients with hyponatremia beyond an isolated single event should be evaluated for their bone density and fracture risk" no matter their age or sex, said senior investigator Dr. Joseph Verbalis, chief of the division on endocrinology and metabolism at Georgetown.
Based on the findings, "we [speculate] that early treatment of hyponatremia will prevent progression of bone disease and decrease fracture risk," and perhaps even obviate the need for bisphosphonates. "It’s an implication that needs to be followed up with definitive studies," he said.
Chronic hyponatremia increases osteoclast proliferation and activity, while recent hyponatremia reduces reaction time and makes it less likely people will catch themselves if they stumble. Elderly people are most at risk, either from overzealous salt restriction, sodium-depleting drugs like thiazide diuretics, or the syndrome of inappropriate antidiuretic hormone secretion (Indian J. Endocrinol. Metab. 2011;15(Suppl3):S208-S215).
The mean age of subjects in the osteoporosis analysis was about 75 years, and almost 90% were women. In the fragility fracture analysis, the mean age was about 60 years, and just over half the subjects were women.
Among the roughly 3 million patients the team initially sampled at the start of their work, there was a more than twofold increase in the prevalence of osteoporosis in hyponatremic (4.6%) vs. nonhyponatremic (1.8%) subjects, and a similar increase in vertebral or long-bone fractures (9.5% vs. 3.7%).
Dr. Verbalis is a consultant, investigator, speaker, and adviser for Otsuka, the maker of the hyponatremia drug tolvaptan. He is also a consultant for Cornerstone Therapeutics and Ferring Pharmaceuticals. The study had no outside funding.